CC-4047 Rocks Again

Three months ago I enrolled in a phase-2 trial (study) of Celgene's new IMiD drug CC-4047, with once-weekly dexamethasone. This third cycle brought another good result. My two primary markers, IgG and M-spike, are both down more than 50% after three months. This is an excellent response, especially since I stopped responding last year to thalidomide, a relative of CC-4047. I know that other patients have done well too. CC-4047 is not a cure for myeloma, but it may become a very important tool in managing it and an actual lifesaver for some who have exhausted other options. I hope it becomes more widely available SOON.

CC-4047 side effects for me:

• Bradycardia - my resting heart rate has dropped from about 48 to about 41.
• Slight reduction in red cell count and hemoglobin, taking both just below the reference range.
• Tinnitus from the aspirin that I take with the CC-4047.

No neuropathy, thromboses, leukopenia, neutropenia, or other difficult side effects yet, though these are all possible.

Dexamethasone side effects:

• "Peppy" and not-so-peppy days, fitful sleep one day a week.
• Increase in belly fat - I'm pretty sure this is happening.
• Loss of muscle mass, especially quads - my running speed is declining.
• High blood sugar levels on "dex day," as measured with glucose monitor.
• Thinning of my skin; it seems quite fragile now.
• Dex voice (tight).

Considering the good response and the dex side effects, Dr. L reduced the dex dosage from 40 mg to 20 mg once weekly for the third cycle just completed. We will continue with 20 mg for the fourth cycle.

I'm lucky, or blessed, in so many ways. Though I can't run as fast as I once could, that's unimportant in the big picture. Most important, myeloma has not yet hurt me. Aside from painless lesions inside three bones, I have no symptoms from the disease itself, and symptoms from the treatment are quite livable thus far. I wish that all myeloma survivors were so lucky, or blessed. Thank you for your prayers, and I offer you mine.

Related links:

• My Myeloma A discussion of my myeloma, not very technical.
• My Treatment History Not technical.
• My Test Charts Graphic displays of several key test results over time.
• My Test Result Table Best with a wide browser window. Very "technical."

Other things that Sunshine and I discussed with Dr. L:

• The loss of muscle mass and the thin skin, both caused by dex, may be reversible if I can ever stop using dex.
• There is not enough information yet on CC-4047, or on its relative Revlimid, to know if either drug is likely to cause other cancers or to change the myeloma to a more aggressive type. So far so good.
• The absolute amount of drop in IgG and M-Spike seems to be somewhat less for each successive cycle, and that trend is likely to continue. It's the direction that is important. I notice that the drop in IgG as a percentage of the previous measurement has been about the same from cycle to cycle, about 25%.
• I expressed the view that since the current treatment is working and there are lots of other treatments available, I might expect not to die from myeloma for five or ten years even without any advances in treatment. Dr. L thought that was not an unrealistic expectation. Cool.
• We talked about running a little too. :-)

A late-arriving result: Dr. L had my blood checked for stored ferritin, with a result of 32 ug/L compared with a reference range of 24 to 336 ug/L. It's on the low side; I need to research this and maybe discuss with my naturopath, Dr. H.



Tonight's celebration salad: Organic romaine, cucumber, organic walnuts, avocado, organic strawberries, blue cheese, organic red wine vinegar, organic pomegranate juice.

Dex and Blood Sugar, Part 3

In early April I did a little experiment, measuring my blood glucose approximately every half hour on three different days: (1) Dex day (after taking dex the night before), (2) the next day, and (3) the fifth day (hopefully no dex). Results are here.

I didn't like that much dex for several reasons, and when I showed the shart to Dr. L she reduced my dex dosage from 40 mg to 20 mg. This week I did the measurements again for "dex day," and found the glucose levels significantly lower, as expected.

Here are averages for each of three different days:

Dex		Glucose mg/dL
40 mg		144.3
20 mg		115.8
None		88.2

Bottom line: 20 mg of dex puts the average glucose approximately midway between 40 mg of dex and no dex. Huh - no surprise.

Here is a TABLE showing actual measurements and times.

Below is a chart. Click to enlarge.

CC-4047 Study at Ten Weeks

Yesterday morning I had the blood draw for ten weeks in the trial of the new drug CC-4047. Here is a table showing several CBC values on four different dates including yesterday:

	SMG	Mayo	Mayo	SMG
CBC	Mar 28	Apr 03	May 01	May 15	Minimum
WBC (leukocytes) K/uL	5.3	7.7	6.0	4.9	2.0
NE# (neutrophils) K/uL	2.6	4.98	3.26	1.7	1.0
PLT (platelets) K/uL	232	303	243	251	50
RBC (erythrocytes) K/uL	4.54	4.42	3.95	4.32
HGB (hemoglobin) K/uL	15.0	15.1	13.5	14.4

SMG = Stillwater Medical Group in Stillwater, MN
Mayo = Mayo Clinic in Rochester, MN

Dr. L at Mayo is especially interested in the top three counts. If the CC-4047 trial drug causes any of those three to fall below its displayed minimum, the protocol will be changed for me, or, eventually, I could even be dropped from the study. Leukocytes are down a bit and neutrophils are down more, actually below the reference range, but both are still within the normal range of fluctuation observed over the past five years. Good.

I am also interested in the other two. RBC and HGB are always near the low edge of the range for me, and in fact RBC is still below the reference range. But it is up slightly, so my non-medical opinion is that it is stable too. Good.

I left out one set of numbers, taken April 18 at Stillwater Medical Group (SMG). Those showed a lower value for WBC than I have ever had in the last five years, and higher values for RBC and HGB than I have had. My local Dr. L at SMG seems to agree that those are NOT my numbers; there was a mixup somewhere. He is also concerned about the OTHER person, who may have gotten MY results, which probably would have shown a sudden movement in the direction of anemia but no problem with the white counts.

Bottom line: Never make an important treatment decision based solely on ONE set of labs, especially if those labs are inconsistent with other recent ones.



Lunch of leftovers: Hearty chicken soup with free-range chicken, organic carrots, organic peas and more; organic brown rice pasta with organic corn, organic tomato and more; free-range bison with onions and organic carrots.

CC-4047 Rocks!

In early March I joined a phase-2 trial (Mayo Clinic study) of Celgene's new IMiD drug CC-4047, with once-weekly dexamethasone. My two primary markers, IgG and M-spike, are both down almost 50% after just two one-month cycles. This is an excellent response, especially considering that I stopped responding to thalidomide, a similar IMiD. Another patient that I know had an even better response on the same study, with markers dropping by half in just the first cycle. I have heard that other patients have done well too.

CC-4047 is not a cure for myeloma, but it may become a very important tool in managing it and, I'm sure, a lifesaver for some who have exhausted other options. I hope that Celgene will do whatever it takes to get it approved soon - people's lives are on the line.

CC-4047 side effects for me:

• Bradycardia - my resting heart rate has dropped from about 48 to about 41.
• Slight reduction in red cell count and hemoglobin, taking RBC just below the reference range.
• Tinnitus from the aspirin that I take with the CC-4047.

No neuropathy, thromboses, leukopenia, neutropenia, or other difficult side effects yet, though these are all possible. Albumin seems low, but other liver markers are normal.

Dexamethasone side effects:

• "Peppy" and not-so-peppy days, fitful sleep one or two days a week.
• Increase in belly fat - I'm pretty sure this is happening.
• Loss of muscle mass, especially quads - my running speed is declining.
• High blood sugar levels on "dex day," as measured with glucose monitor.
• Dex voice (tight).

Considering the good response and the dex side effects, Dr. L has changed the dex dosage from 40 mg to 20 mg once weekly. And the study continues, now well into the first week of the third cycle.

I'm lucky, or blessed, in so many ways. Most important, myeloma has not yet hurt me. Aside from painless lesions inside three bones, I have no symptoms from the disease itself, and symptoms from the treatment are quite modest thus far. I wish that all myeloma survivors were so lucky, or blessed. Thank you for your prayers, and I offer you mine.

Related links:

• My Myeloma A discussion of my myeloma, not very technical.
• My Treatment History Not technical.
• My Test Charts Graphic displays of several key test results over time.
• My Test Result Table Best with a wide browser window. Very "technical."

Free-range no-hormone no-antibiotic chicken, organic chard with dried cranberries, macadamia nuts, organic apple, organic pomegranate juice.

Lucky Don

If you skip over the fact of the cancer, I'm a very fortunate guy. The CC-4047 trial is so far very successful for me. After the first one-month cycle, IgG dropped from 2960 to 2230, and after the second cycle it is now 1610. Similarly, M-spike dropped from 2.7 to 1.9, and now to 1.4. This brings my markers back two to three years in just two months.

Best of all, side effects have been quite modest so far, the worst coming from the dexamethasone, not the CC-4047. The regimen will continue for another cycle, probably many cycles, but at half the dose of dex.

I am VERY happy!. Time for celebration. Much more to say about the results and my conversation with Dr. L, but no time to post it tonight. Big weekend coming, so it may be next week before I can bring it all together.

Drug Study at Six Weeks

This morning was the end of six weeks in the trial of the new drug CC-4047. Here is a table showing several CBC values on four different dates including today:

	SMG	SMG	Mayo	SMG
CBC	Mar 21	Mar 28	Apr 03	Apr 18	Minimum
WBC (leukocytes) K/uL	5.8	5.3	7.7	3.6	2.0
NE# (neutrophils) K/uL	2.9	2.6	5.0	1.8	1.0
PLT (platelets) K/uL	245	232	303	148	50
RBC (erythrocytes) K/uL	4.28	4.54	4.42	5.52
HGB (hemoglobin) K/uL	14.3	15.0	15.1	18.5
Albumin g/dL			3.4	3.5

The top three counts are ones that Mayo is particularly interested in watching, because the CC-4047 trial drug may eventually drive those numbers down. If any of those three counts falls below its minimum, the protocol will be changed for me, or, eventually, I could even be dropped from the study. Sorry to say, every one of those counts has dropped dramatically in just two weeks, though they are all still well above their minimum values.

I am also interested in the other three. HGB (hemoglobin) is slightly out of the top of its range. I don't know what to make of that. In fact, both HGB and RBC (red cell count) are higher than I have ever seen them in five years of tabulating results. They're nothing to worry about, but they don't seem like my blood. I'm actually wondering about a lab error.

Albumin, on the other hand, is almost exactly what it was two weeks ago at Mayo, and it is at the lowest I have seen in the five years. More to discuss with Dr. Lacy in a couple of weeks, when we will do the tests again. Albumin is one of the liver-function indicators, and is right on the boundary where the International Staging System would place a newly-diagnosed patient in Stage II rather than Stage I.

Bottom line: Albumin makes sense, though I don't like it much. The others seem wacko for me. I do believe that the albumin blood was drawn into a different tube than the CBC blood, so there is the possibility of a lab mixup in one and not the other. I sort of hope so.



Recent salad: Organic romaine lettuce with cucumber, organic dried sour cherries, blue cheese, salted pistachios, clementine, organic red wine vinegar.

Results of Cycle 1

Today was my 28-day (first cycle) checkup at Mayo for the phase II trial of CC-4047 with dexamethasone. The idea is to make sure that the drugs are not hurting me, though it would also be nice if they were already helping.

Dr. Lacy was away at a conference so I saw Dr. Buadi, another very likeable and knowledgeable doctor.

All of the closely-watched markers of possible harm from the drugs are normal. Yay! Further, IgG was down 25% and M-spike was down 30% in just 28 days. That is very good. The only significant “bad” news was a decrease in albumin, down to the very bottom edge of the reference range, though just within it. I didn't have a chance to discuss this with the doctor today, but I will call tomorrow. Actual values from key tests are displayed graphically in charts and numerically in a test result table, see links below.

I am still on the trial drug and would have started the second 28-day cycle Friday night. However, I am going to stop for two days and start that cycle on Sunday night instead, so that I will not be feeling the effects of dexamethasone on the weekends when I race.
Related links:

• My Myeloma A discussion of my myeloma, not very technical.
• My Treatment History Not technical.
• My Test Charts Graphic displays of several key test results over time.
• My Test Result Table Best with a wide browser window. Very "technical."

I was still hungry after dinner tonight - this fixed it. Watermelon, blueberries, organic apple, pineapple, organic yogurt, Dove dark chocolate Easter egg.

Dex and Blood Sugar, Part 2

Well, this experiment is complete, or as nearly so as it will get. I took blood glucose measurements on three days: (1) Saturday, after taking 40 mg of dexamethasone Friday at bedtime; (2) Sunday, the next day, and (3) Wednesday, the fifth day. Here are average blood glucose measurements for the three days:

Sat:		144.3 mg/dL
Sun:		101.2 mg/dL
Wed:		88.2 mg/dL

Bottom line: Assuming that Wednesday's measurements were "normal," then Sunday's were at least 10 points higher than normal and Saturday's were more than 50 points higher! This is "low-dose" dex - it's no wonder that high-dose dex gives people the symptoms of diabetes and sometimes even gives them the real thing.

Here is a TABLE showing actual measurements and times. It also has links to photos of the meals that were eaten.

Below is a chart of the same thing. Click to enlarge.

Dex and Blood Sugar, Part 1

We myelomiacs are all aware that dexamethasone (dex) can cause type II diabetes, sometimes permanent and sometimes reversible after discontinuing dex. This is most common among people who have taken "high-dose" dex, typically 40 mg per day four days on and four off.

I am taking "low-dose" dex, 40 mg once a week, Friday night before I go to bed. Nevertheless I already have a blood glucose monitor which I bought for another reason (not diabetes) and wanted to see what happens to my own blood sugar when I take dex. I decided to take a measurement about every half hour between waking and bedtime on three days: (1) Saturday, the day after taking dex, also called "buzz" day; (2) Sunday, "recovery" day; and (3) Wednesday, the fifth day, when effects from dex should be minimal.

The graph will be much easier to read if you click on it to enlarge it.


Here is a table with the actual numbers, exact times, and comments.

This experiment is only two thirds complete, but already somewhat instructive. I couldn't wait to post:

• About two years ago I ran a similar experiment for different reasons, and got an average reading of 104 mg/dL over parts of three days.
• Saturday's average reading was 144 mg/dL, much higher.
• None of my readings quite reached 200, which some say can be a signal of diabetes.
• Sunday's (today's) average is 101, even with big meals, much lower than Saturday.
• Glucose pretty much went up after eating carbohydrates, then down again, but with a few surprises:
  • The highest Saturday spike, 193, was measured shortly after finishing a big oatmeal breakfast with fruit and juice.
  • Later, a large serving of homemade chocolate fudge pudding, about 270 calories, seemed to raise glucose by only about 10 points. Are chocolate and milk able to slow absorption of sugars?
  • Still later, a slice of gluten-free bread with honey seemed to raise glucose by about 20 points.
  • All but one of Sunday's readings were lower than the lowest reading of Saturday.

I'll post about this again after Wednesday's test.

Drug Study Day 21

I am on a study of the new drug CC-4047, with once-weekly dexamethasone. This morning was the third weekly blood draw, results already by fax. Here is a table showing several CBC values on four different dates:

	Mayo	SMG	SMG	SMG
CBC	Mar 3	Mar 14	Mar 21	Mar 28	Minimum
WBC (leukocytes) K/uL	5.6	4.8	5.8	5.3	2.0
NE# (neutrophils) K/uL	3.5	2.1	2.9	2.6	1.0
PLT (platelets) K/uL	211	220	245	232	50
RBC (erythrocytes) K/uL	4.62	4.50	4.28	4.54
HGB (hemoglobin) K/uL	15.4	14.9	14.3	15.0

The top three counts are ones that Mayo is particularly interested in watching, because the CC-4047 trial drug may eventually depress those numbers. If any of those three counts falls below its minimum, the protocol will be changed for me, or, eventually, I could even be dropped from the study.

No problems yet. The three key counts are all down slightly from last week, but still higher than two weeks ago. Red blood count (RBC) was a little low last week, back in range today.

Dexamethasone again tonight.


Recent dinner salad: Organic romaine lettuce with sliced cucumber, blueberries, cashews, blue cheese, corn bread, clementine, organic apple cider vinegar.

Day 15

I went into the local clinic this morning for the second weekly blood draw, and received the results by fax. Here is a table showing several CBC values on four different dates:

	MOHPA	Mayo	SMG	SMG
CBC	Dec 26	Mar 3	Mar 14	Mar 21	Minimum
WBC (leukocytes) K/uL	3.9	5.6	4.8	5.8	2.0
NE# (neutrophils) K/uL	2.2	3.5	2.1	2.9	1.0
PLT (platelets) K/uL	188	211	220	245	50
RBC (erythrocytes) K/uL	4.44	4.62	4.50	4.28
HGB (hemoglobin) K/uL	14.4	15.4	14.9	14.3

The top three counts are ones that Mayo is particularly interested in watching, because the CC-4047 trial drug may eventually depress those numbers, as does the analogue drug Revlimid. The minimum counts shown are well below the reference range in each case, and if any of those three counts falls below its minimum the protocol will be changed for me, or, eventually, I could even be dropped from the study.

But no problems yet. The three key counts are all UP, actually. That's very good news.

Red blood count (RBC) is slightly below the reference range, but this has happened before. My RBC is always at the low end. I do wonder why that is - shouldn't a runner's system create EXTRA red cells to carry the oxygen that s/he needs when consuming 700-800 calories per hour? Guess not, in my case, but if it did then maybe I could run faster :-) Anyway, hemoglobin (HGB) is nicely within the reference range, so I'm not concerned.

My doctor ordered two extra tests this time: (1) Prothrombin time (PROTIME) with International Normalized Ratio (INR). This is a measure of the time it takes for the blood to clot under specific laboratory conditions. PROTIME is specific to the particular laboratory and the conditions that it sets, and INR is calculated from the result based on those conditions. Happily, my INR is 1.0 and PROTIME is 9.9, very close to the center of the reference range for this lab; and (2) Partial Thromboplastin Time, for which the result was 26.9, also quite normal. No warfarin for me unless a clot shows up.

Dexamethasone tonight - I should be on my game tomorrow!



This morning's breakfast: Irish oatmeal with organic flame raisins, Sunshine's teff bread with dates and nuts, dried dragon fruit, organic walnuts, Don's nut/fruit/berry mix, banana, organic nonfat milk.


Today's lunch: Organic brown rice pasta with homemade organic pasta sauce and parmesan cheese, naval orange, organic vegetable mix, organic pure pomegranate juice.


Recent dinner: Free-range no-hormone no-antibiotic bison, clementine, organic squash with organic salsa, Sunshine's teff bread with dates and nuts, local honey, organic sweet corn, Dove dark chocolate.

Bone-Strengthening Exercises

Tuesday I spent an hour with Angie, our personal trainer. She knows that I have myeloma and that there is active disease in both shoulder blades and in the T10 vertebra, weakening those bones. I asked her to show me some exercises for strengthening the muscles in my back, because we know that bones will strengthen themselves wherever the muscles that attach to them are strengthened.

In that hour she showed me some lower-body stretches in addition to those that I already do, to improve my running. Then she gave me five upper-body exercises, which I tried this morning for the first time at home:

• Reverse Fly: The focus is on the back part of the shoulders. Equipment: Resistance band attached to a fixed object. Start with the band in hand at the opposite hip, keeping arm straight swing hand from hip across the body to shoulder height on the other side. Try to keep trapezius muscles (traps) relaxed. Three sets of 12 repetitions (reps). Alternative method (from the internet): work one arm against the other, see graphic. I tried this alternative today.

• Cable Row: Simulated rowing. Face toward a weighted cable or resistance band, pull both elbows backward to bring the handle to the body, keep shoulders down, imagine trying to grasp a marble between shoulder blades. Slowly return. Three sets of 12 reps.
• Stability Ball Push-Back: Lay on back on stability ball holding a 10-lb medicine ball against the stomach, bend knees and slide down to bring butt to heels, then push back up. I'm not sure what this exercise is for, actually, because I feel it primarily in the quads. I'll have to set up another appointment and ask Angie. Three sets of 12.
• Assisted Pullup: A pullup is the same as a chinup except with palms facing away instead of toward me. I can do unassisted pullups (at least one, I tried it) but that may put my back at risk so we're going with assisted pullups which do not require me to lift my entire weight. At the gym, there is a machine for doing this with a very precise amount of assist. At home, today, I put a chair under the pullup bar, which brought my chin right to the bar at full height, and then used my legs to provide an assist. See the small graphic, where that same principle is applied but the bar is lower, making the chair unnecessary. The amount of assistance is uncalibrated, but it seemed to work fine. Three sets of 8 to 10.
• Stability Ball Cobra: This is a sort of "reverse crunch" using the back muscles instead of the muscles in front of the body. Lay stomach-down on the stability ball, feet against the wall for stability. Cross arms, slowly let upper body down as far as it will go, slowly raise again, but only until body is straight. Pull shoulders back, again grabbing the imaginary marble with the shoulder blades. Three sets of 8 to 10.

That was ONE hour with Angie. No doubt the list of possible and beneficial exercises is incomplete, as my understanding certainly is. Hopefully, by blogging about these and (therefore) looking each of them up on the internet I will learn enough to make them stick in my alleged mind. But I suspect that our family will need a few more sessions with Angie to get everything right.

After the session we stopped at Target to pick up a nice 65-cm stability ball and a couple of resistance bands. We already had a pullup bar, and that's all I needed for this morning's routine.